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miR146a up-regulation is involved in small HA oligosaccharides-induced pro-inflammatory response in human chondrocytes.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.bbagen.2020.129731
Angela Avenoso 1 , Angela D'Ascola 2 , Michele Scuruchi 2 , Giuseppe Mandraffino 2 , Salvatore Campo 1 , Giuseppe M Campo 2
Affiliation  

Background

Small HA fragments are produced during cartilage degradation and their role seems to be preponderant during pathologies in which cartilage injury contribute to trigger and perpetuate the inflammatory mechanism.

Several reports have increasingly shown that MicroRNAs (miRs), a small non-coding mRNAs are involved in the regulation of multiple biological processes, including cell proliferation and inflammation response in different pathologies, among them miR146a seems to be involved in inflammatory processes.

Methods

Starting by these evidences we investigated the levels of miR146a and its correlation with inflammatory mediators in an experimental model of 6-mer HA-induced inflammatory response in human cultured chondrocytes.

Results

Treatment of chondrocytes with 6-mer HA showed up-regulation in inflammation parameters such as TLR-4, and CD44 receptors activation, IL-6, IL-1β and MMP-13 mRNA expression and proteins production, as well as NF-kB activation. We also revealed an up-regulation of miR146a. Transfection with a miR146a mimic or miR146a inhibitor produced the following effects: chondrocytes receiving miR146a mimic and then 6-mer HA significantly reduced inflammatory cytokines and MMP-13, while exposition of chondrocytes with miR146a inhibitor and then the 6-mer HA incremented the activity of damaging cytokines and MMP13. Expression of CD44 receptor was not affected by miR-146a treatments, while TLR-4 expression and NF-kB activation were modified.

Conclusions

We concluded that up-regulation of miR146a occurred in 6-mer HA-induced inflammation response may reduce the inflammatory cascade by modulating TLR-4 and NF-kB activation.

General significance

These results could be useful in develop new therapeutic strategies with the aim to reduce OA and RA incidence.



中文翻译:

miR146a的上调与人软骨细胞中小HA寡糖诱导的促炎反应有关。

背景

小HA片段是在软骨降解过程中产生的,它们的作用似乎在病理学中占主导地位,在这种病理中,软骨损伤有助于触发并永久维持炎症机制。

越来越多的报道表明,微小的非编码mRNA MicroRNA(miRs)参与多种生物过程的调控,包括不同病理学中的细胞增殖和炎症反应,其中miR146a似乎参与了炎症过程。

方法

从这些证据出发,我们在人类培养的软骨细胞中由6-mer HA诱导的炎症反应的实验模型中,研究了miR146a的水平及其与炎症介质的相关性。

结果

用6-mer HA处理软骨细胞显示炎症参数如TLR-4和CD44受体激活,IL-6,IL-1β和MMP-13 mRNA表达和蛋白质产生以及NF-kB激活上调。我们还发现了miR146a的上调。用miR146a模仿物或miR146a抑制剂转染可产生以下效果:接受miR146a模仿物然后6聚体HA的软骨细胞显着减少了炎性细胞因子和MMP-13,而用miR146a抑制剂暴露于软骨细胞,然后6聚体HA增加了软骨细胞的活性。破坏性细胞因子和MMP13。CD44受体的表达不受miR-146a处理的影响,而TLR-4表达和NF-kB激活被修饰。

结论

我们得出结论,miR146a的上调发生在6-mer HA诱导的炎症反应中,可能通过调节TLR-4和NF-kB激活而减少了炎症级联反应。

一般意义

这些结果可能有助于开发新的治疗策略,以减少OA和RA的发生。

更新日期:2020-09-26
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